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A - Regimen Name

BEACOPP Regimen
Bleomycin-Etoposide-ADRIAMYCIN ® (DOXOrubicin)-Cyclophosphamide-ONCOVIN ® (VinCRIStine)-Procarbazine-Prednisone


Disease Site
Hematologic - Lymphoma - Hodgkin

Intent
Curative

Regimen Category
Evidence-Informed :

Regimen is considered appropriate as part of the standard care of patients; meaningfully improves outcomes (survival, quality of life), tolerability or costs compared to alternatives (recommended by the Disease Site Team and national consensus body e.g. pan-Canadian Oncology Drug Review, pCODR).  Recommendation is based on an appropriately conducted phase III clinical trial relevant to the Canadian context OR (where phase III trials are not feasible) an appropriately sized phase II trial. Regimens where one or more drugs are not approved by Health Canada for any indication will be identified under Rationale and Use.


Rationale and Uses

Treatment of unfavourable or advanced stage Hodgkin's lymphoma, in patients who are 15-65 years of age.


Supplementary Public Funding

procarbazine
ODB - General Benefit (procarbazine)

prednisone
ODB - General Benefit (prednisone)

 
B - Drug Regimen

cyclophosphamide
1250 mg /m² IV Day 1
DOXOrubicin
35 mg /m² IV Day 1
etoposide
200 mg /m² IV Days 1 to 3
procarbazine
100 mg /m² PO Daily, on days 1-7
(Outpatient prescription in multiples of 50mg capsules)
prednisone
40 mg /m² PO Daily, on days 1-14
(Outpatient prescription in multiples of 5 mg and 50 mg tablets)
vinCRIStine
1.4 mg /m² IV (max 2 mg) Day 8
bleomycin
10 units /m² IV Day 8
filgrastim
Use as primary prophylaxis.
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C - Cycle Frequency

REPEAT EVERY 21 DAYS

For a usual total of 6 to 8 cycles unless disease progression or unacceptable toxicity occurs

 
D - Premedication and Supportive Measures

Antiemetic Regimen:

Moderate (D1-7)
Minimal (D8)


Febrile Neutropenia Risk:

High

Other Supportive Care:

  • Consider measures to preserve fertility or sperm/ovum banking.

Also refer to CCO Antiemetic Recommendations.

 
E - Dose Modifications

Doses should be modified according to the protocol by which the patient is being treated.

Dosage with toxicity

On day 1 of cycle, platelets must be ≥ 100 x 109/L and ANC ≥ 1 x 109/L and toxicities recovered to ≤ grade 2.

Dose Levels:

 

Dose level 1

(standard BEACOPP)

Dose level 2

Dose level 3

Dose level 4

Dose level 5

(escalated BEACOPP)

Doxorubicin

25

35

35

35

35

Cyclophosphamide

650

800

950

1100

1250

Etoposide

100

125

150

175

200

Dosage with Toxicity:

Toxicity (Counts x 109/L or Grade)1

Action (dose level or % previous dose)

Grade 4 AGC  >4 days   
Grade 4 platelets 
Febrile neutropenia
↓ 1 dose level 2

Grade 4 GI

↓ 1 dose level 2

Delay > 2 weeks

↓ 2 dose levels or ↓ to standard BEACOPP (dose level 1)

Treatment delay of 1-2 weeks

↓ 1 dose level 2

Grade 3 other toxicity

Consider ↓ 1 dose level
Grade 4 other toxicity
Discontinue or ↓ 1 to 2 dose levels
Cardiotoxicity3

Discontinue doxorubicin

1On day 1 of cycle, platelets must be ≥ 100 x 109/L and ANC ≥ 1 x 109/L and toxicities recovered to ≤ grade 2.

2If toxicity requiring dose decrease/delay recurs on next cycle, reduce to dose level 1.  If recurs at other cycles, reduce by 2 dose levels.

3including any signs and symptoms of heart failure, greater than 10% decline in LVEF to below the lower limit of normal, a greater than 20% decline in LVEF from any level, or LVEF ≤ 45%.

 

 

Neurotoxicity:

Symptom
% usual dose of Vincristine
areflexia only
100 %
abnormal buttoning, writing
67 %
moderate motor neuropathy (± cranial)
Hold until recovery then reduce dose by 50%
severe motor neuropathy
Omit



Hepatic Impairment

AST/ALT
Bilirubin
Bleomycin
Etoposide
Doxorubicin
Cyclophosphamide
Vincristine
Procarbazine
    (% previous dose)
 
1-2 x ULN
No change
50%
50%
No change
50%
75%
5-10 x ULN
> 2 - 4 x ULN
No change
25%
25%
Caution
25%
OMIT

> 10 x ULN

> 4 x ULN
No change
OMIT
OMIT
Caution
OMIT
OMIT

Renal Impairment

Creatinine Clearance (mL/min)
Bleomycin
Etoposide
Doxorubicin
Cyclophosphamide
Vincristine
Procarbazine
  (% previous dose)
>30-50
75%

No change

No change

50-75%

No change

Consider dose reduction

10-30
75%

No change

No change

50% or OMIT

No change

Consider dose reduction

<10
50%

50% or OMIT

No change

OMIT

No change

Consider dose reduction or OMIT


Dosage in the Elderly

No dose modification routinely required for cyclophosphamide, but should be used with caution.  Use doxorubicin with caution. No dose adjustment required for etoposide.  Older patients may have more neurotoxicity with vincristine.

 

 


 
F - Adverse Effects

Refer to cyclophosphamide, DOXOrubicin, etoposide, procarbazine, prednisone, vinCRIStine, bleomycin, filgrastim drug monograph(s) for additional details of adverse effects


Most Common Side Effects

Less Common Side Effects, but may be Severe

·           

  • Alopecia
  • Nausea, vomiting
  • Myelosuppression ± infection, bleeding (may be severe)
  • Diarrhea/constipation
  • Mucositis
  • ↑ LFTs
  • Dizziness 
  • GI irritation (may be severe, including perforation) 
  • Hyperglycemia
  • Insomnia
  • Muscle weakness
  • Phlebitis, vesicant
  • Neuropathy (may be severe)
  • Hemorrhagic cystitis
  • Reproductive risk

        

  • Hypersensitivity
  • Hyperuricemia
  • Adult respiratory distress syndrome (ARDS)
  • Pneumonitis
  • Arterial thromboembolism
  • Venous thromboembolism
  • CNS effects
  • Glaucoma
  • Cardiotoxicity
  • Nephrotoxicity
  • Pancreatitis
  • Secondary malignancy
  • Radiation recall
  • Rash
  • DIC/HUS/hemolysis
 
G - Interactions

Refer to cyclophosphamide, DOXOrubicin, etoposide, procarbazine, prednisone, vinCRIStine, bleomycin, filgrastim drug monograph(s) for additional details

 
H - Drug Administration and Special Precautions

Refer to cyclophosphamide, DOXOrubicin, etoposide, procarbazine, prednisone, vinCRIStine, bleomycin, filgrastim drug monograph(s) for additional details


 

 

 
I - Recommended Clinical Monitoring

Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.

Recommended Clinical Monitoring

  • Clinical toxicity assessment (including local toxicity, urogenital, GI, neurotoxicity, bleeding tendency, cardiotoxicity and pulmonary); at each visit
  • CBC; baseline and before each cycle. Interim counts should be done in first cycle and repeated if dose modifications necessary.
  • Blood glucose testing; baseline and regular.
  • Regular chest x-ray and routine pulmonary function test
  • Baseline and regular liver and renal function tests (including electrolytes and magnesium), and urinalysis.
  • Cardiac examination especially with risk factors (including prior therapy with Epirubicin, Mitoxantrone, and other cardiotoxic drugs), or a cumulative doxorubicin dose of > 450mg/m2.
  • Baseline blood pressure at each treatment; monitor for hypotension.
  • Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version


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J - Administrative Information

Prednisone, Procarbazine, Filgrastim:  Outpatient prescription for home administration


Approximate Patient Visit
Day 1: 2 hours; Days 2, 3: 1 hour; Day 8: 0.5 hour
Pharmacy Workload (average time per visit)
22.114 minutes
Nursing Workload (average time per visit)
43.729 minutes
 
K - References

Diehl V, Franklin J, Hasenclever D, et al. BEACOPP, a New Dose-Escalated and Accelerated Regimen, Is at Least as Effective as COPP/ABVD in Patients With Advanced-Stage Hodgkin's Lymphoma: Interim Report From a Trial of the German Hodgkin's Lymphoma Study Group.  J Clin Oncol 1998;16:3810-21.

Diehl V, Franklin J, Pfreundschuh M, et al.Standard and Increased-Dose BEACOPP Chemotherapy Compared with COPP-ABVD for Advanced Hodgkin’s Disease. N Engl J Med 2003;348:2386-95.

Engert A, Diehl V, Franklin J, et al.  Escalated-Dose BEACOPP in the Treatment of Patients With Advanced-Stage Hodgkin’s Lymphoma: 10 Years of Follow-Up of the GHSG HD9 Study. J Clin Oncol 2009;27:4548-4554.

Federico M, Luminari S, Iannitto E, et al.  ABVD Compared With BEACOPP Compared With CEC for the Initial Treatment of Patients With Advanced Hodgkin’s Lymphoma: Results From the HD2000 Gruppo Italiano per lo Studio dei Linfomi Trial. J Clin Oncol 2009;27:805-811.

Tesch H, Diehl V, Lathan B, et al.  Moderate Dose Escalation for Advanced Stage Hodgkin’s Disease Using the Bleomycin, Etoposide, Adriamycin, Cyclophosphamide, Vincristine, Procarbazine, and Prednisone Scheme and Adjuvant Radiotherapy: A Study of the German Hodgkin’s Lymphoma Study Group. Blood 1998;92:4560-4567.

June 2019 Updated drug links


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M - Disclaimer

Regimen Abstracts
A Regimen Abstract is an abbreviated version of a Regimen Monograph and contains only top level information on usage, dosing, schedule, cycle length and special notes (if available). It is intended for healthcare providers and is to be used for informational purposes only. It is not intended to constitute or be a substitute for medical advice, and all uses of the Regimen Abstract are subject to clinical judgment. Such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability, and Cancer Care Ontario disclaims all liability for the use of this information, and for any claims, actions, demands or suits that arise from such use.
Information in regimen abstracts is accurate to the extent of the ST-QBP regimen master listings, and has not undergone the full review process of a regimen monograph.  Full regimen monographs will be published for each ST-QBP regimen as they are developed.
Regimen Monographs
Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.
The information set out in the drug monographs, regimen monographs, appendices and symptom management information (for health professionals) contained in the Drug Formulary (the "Formulary") is intended for healthcare providers and is to be used for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects of a particular drug, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for a given condition. The information in the Formulary is not intended to constitute or be a substitute for medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.
The format and content of the drug monographs, regimen monographs, appendices and symptom management information contained in the Formulary will change as they are reviewed and revised on a periodic basis. The date of last revision will be visible on each page of the monograph and regimen. Since standards of usage are constantly evolving, it is advised that the Formulary not be used as the sole source of information. It is strongly recommended that original references or product monograph be consulted prior to using a chemotherapy regimen for the first time.
Some Formulary documents, such as the medication information sheets, regimen information sheets and symptom management information (for patients), are intended for patients. Patients should always consult with their healthcare provider if they have questions regarding any information set out in the Formulary documents.
While care has been taken in the preparation of the information contained in the Formulary, such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability.
CCO and the Formulary’s content providers shall have no liability, whether direct, indirect, consequential, contingent, special, or incidental, related to or arising from the information in the Formulary or its use thereof, whether based on breach of contract or tort (including negligence), and even if advised of the possibility thereof. Anyone using the information in the Formulary does so at his or her own risk, and by using such information, agrees to indemnify CCO and its content providers from any and all liability, loss, damages, costs and expenses (including legal fees and expenses) arising from such person’s use of the information in the Formulary.